基于网络药理学与体外实验探究蒙药古日古木-13降脂作用机制*

作者：张 杰，石佳林，张海峰

单位：内蒙古医科大学基础医学院，内蒙古 呼和浩特 010050

引用：引用：张杰，石佳林，张海峰.基于网络药理学与体外实验探究蒙药古日古木-13降脂作用机制[J].中医药导报,2025,31(11):38-44.

DOI：10.13862/j.cn43-1446/r.2025.11.007

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摘要：

目的：运用网络药理学方法研究蒙药古日古木-13治疗高脂血症的活性成分和作用机制，并通过分子对接和细胞实验进行验证。方法：利用TCMSP、PubChem、Swiss Target Prediction、PharmMapper等数据库筛选出古日古木-13治疗高脂血症的活性成分及其作用靶点，挖掘GeneCard、OMIM数据库中高脂血症疾病靶点，采用DAVID数据库进行GO富集分析和KEGG通路富集分析，并利用Cytoscape构建“成分-靶点-通路”网络，最后运用Autodock 4.2软件对活性成分和靶点进行分子对接验证。培养并诱导3T3-L1细胞分化为脂肪细胞，通过MTT和油红O染色检测药物对细胞活力和脂滴积累的影响，同时通过qPCR实验检测关键基因表达。结果：筛选获得古日古木-13的核心活性成分为鞣花酸、诃子次酸、白果内酯、小檗碱、6-羟基山柰酚。筛选出疾病与药物的交集靶点460个，对交集靶点通过构建蛋白互作分析网络，并对网络进行拓扑学分析筛选获得PIK3CA、Akt1、STAT3、TNF等核心作用靶点；对交集靶点进行GO、KEGG富集分析发现，过程涉及多个脂质代谢相关过程。对分析结果进行分子对接验证发现具有良好对接活性，且细胞实验证明古日古木-13可以减少脂质积累、减少细胞TG含量、增加细胞葡萄糖利用率，增加细胞中PI3K、Akt、PGC-1α基因表达。结论：古日古木-13能够有效治疗高脂血症并缓解细胞脂质积累，其机制可能为通过鞣花酸、诃子次酸、白果内酯、小檗碱等多个活性成分、多靶点、多途径作用对脂质代谢、PI3K、Akt、PGC-1等核心靶点进行调节，达到减少细胞脂质积累、调节脂代谢，进而缓解高脂血症的作用。

关键词：高脂血症；蒙药古日古木-13；网络药理学；靶点

Abstract：

Objective: To study the active ingredients and mechanism of Mongolian medicine Gurigumu-13 in the treatment of hyperlipidemia by network pharmacology, and to verify it by molecular docking and cell experiments. Methods: TCMSP, PubChem, Swiss Target Prediction, PharmMapper and other databases were used to screen out the active ingredients and targets of Gurigumu-13 in the treatment of hyperlipidemia, and the disease targets of hyperlipidemia were mined from GeneCard and OMIM databases. DAVID database was used for GO enrichment analysis and KEGG pathway enrichment analysis, and Cytoscape was used to construct the "component-target-pathway" network. Finally, Autodock 4.2 software was used to verify the molecular docking between active ingredients and targets. 3T3-L1 cells were cultured and induced to differentiate into adipocytes. The effects of Gurigumu-13 on cell viability and lipid drop accumulation were detected by MTT and oil red O staining, and the expression of key genes was detected by qPCR. Results: The core active components of Gurigumu-13 were screened and obtained as ellagic acid, chebulic acid, bilobalide, berberine and 6-hydroxykaanthol. A total of 460 intersection targets of diseases and drugs were screened. The intersection targets were identified by constructing protein interaction analysis network, and the core action targets such as PIK3CA, Akt1, STAT3 and TNF were obtained by topology analysis and screening of the network. GO and KEGG enrichment analysis of intersection targets showed that the process involved several lipid metabolism related processes. Molecular docking verification of the analysis results showed that Gurigumu-13 had good docking activity, and cell experiments showed that Gurigumu-13 could reduce lipid accumulation, reduce cell TG content, increase cell glucose utilization, and increase the expression of PI3K, Akt, and PGC-1α genes in cells. Conclusion: Gurigumu-13 can effectively treat hyperlipidemia and alleviate cellular lipid accumulation. Its mechanism is likely mediated through multiple active ingredients such as ellagic acid, chebulic acid, bilobalide, and berberine. This multi-component, multi-target, and multi-pathway approach acts by regulating core targets involved in lipid metabolism, including PI3K, Akt, and PGC-1α, to reduce cellular lipid accumulation and modulate lipid metabolism, thereby alleviating hyperlipidemia.

Key words：hyperlipidemia; Mongolian medicine Gurigumu-13; network pharmacology; target point

发布时间：2025-11-29

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